Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III)

Phase 2

Completed

• Conditions: Chronic Heart Failure
• Interventions: Drug: Splanchnic nerve block

• Registration Number: NCT04575428
• Lead Sponsor: Duke University

Brief Summary

Splanchnic vasoconstriction may contribute to decompensation of chronic heart failure (HF) via volume redistribution from the splanchnic vascular bed to the central compartment. This is a sympathetically mediated reflex and can be interrupted through a splanchnic nerve block (SNB). We hypothesize that interruption of the efferent/afferent innervation of the splanchnic vasculature will decrease cardiac congestion in patients presenting with HF. Based on preliminary safety and efficacy data in acute and chronic heart failure patients with temporary (\<24 h) SNB. Now we will apply a prolonged SNB in chronic heart failure patients using a long acting agent. We will test the effects of SNB on long term exercise capacitance.

Detailed Description

Activation of splanchnic nerves results in vasoconstriction and reduces splanchnic capacitance, therefore recruiting blood volume into the central circulation. In heart failure, a reduced splanchnic vascular capacitance could be the mechanism underlying symptoms of exercise intolerance and could predispose to rapid decompensation with external fluid intake or retention. A compromised vascular reservoir is likely unable to buffer shifts of fluid and actively contributes to the acute or chronic expulsion of fluid from the splanchnic vascular compartment to the central thoracic compartment. The redistribution of blood volume into the central circulation may lead to a sudden rise in pulmonary and left-sided cardiac pressures in HF. This makes the splanchnic vascular compartment an attractive target in heart failure. Our preliminary proof-of-concept work in patients with acute decompensated and chronic heart failure showed promise for the concept of splanchnic nerve modulation in heart failure. In a series of two small first-in-human studies for acute decompensated heart failure (N=13) (NCT02669407) and chronic heart failure (N=17) (NCT03453151), we found that a splanchnic nerve block (SNB) with lidocaine (90 min duration of action) and ropivacaine (24 hours duration of action) acutely reduced resting and exercise-induced intra-cardiac filling pressures, associated with improved patient symptoms and functional capacity.

The present study will be a prospective open-label pilot study to help establish feasibility, safety and enable dose finding for botulinumtoxin. Following a baseline invasive (right heart catheterization) cardiopulmonary exercise testing (CPX) patients will undergo unilateral celiac plexus block, followed by repeat hemodynamic testing. Functional testing at baseline and follow up will be supplemented by measures of blood volume and autonomic tone.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations
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Related News

Study Timeline

• Study Start: 2020-02-05
• Study First Submitted: 2020-08-20
• Study First Submitted QC: 2020-10-02
• Study First Posted: 2020-10-05
• Primary Completion: 2021-06-16
• Study Completion: 2021-06-16
• Status Verified: 2023-05
• Results First Submitted: 2023-05-19
• Results First Submitted QC: 2023-05-19
• Results First Posted: 2023-06-15
• Last Update Submitted: 2023-06-21
• Last Update Posted: 2023-06-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• Followed at DUMC for known or suspected diagnosis of HF (NYHA stage 2-4, Class C-D), including patients on inotropic medication
• Systolic blood pressure (SBP) > 100 mmHg
• History of HF hospitalization or ER visit or iv diuretic use in last 12 months.
• Patients will be included regardless of left ventricular ejection fraction.

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Exclusion Criteria

• Anticoagulation at the time the procedure or in case of recent warfarin use an INR >1.4. Anticoagulation includes: warfarin, or novel oral anticoagulants like dabigatran, rivaroxaban, apixaban, endoxaban or full dose intravenous heparin products or bivalirudin and fondaparinux). Antiplatelet agents besides aspirin such as ticagrelor, prasugrel, Plavix are also considered to be a contraindication if used at time point of procedure.
• Immunosuppressive medications for solid organ transplant
• Acute MI (STEMI or Type I NSTEMI) within 7 days?
• Evidence of progressive cardiogenic shock within 48 hours
• Restrictive cardiomyopathy
• Constrictive pericarditis
• Pericardial effusion with evidence of tamponade
• Severe valvular stenosis requiring intervention
• Known history of an increased bleeding risk
• Thrombocytopenia (< 50,000)
• End-stage renal disease CKD stage 5 due to primary renal pathology

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Splanchnic nerve block	Splanchnic nerve block	-

Primary Outcome Measures

Name	Time	Method
Absence of Nerve Block Related Complications	8 weeks	Assessment of orthostasis, gastrointestinal symptoms were observed
Peak Exercise Wedge Pressure	4 weeks	Measured with cardiopulmonary exercise testing
Peak Pulmonary Arterial Pressure	4 weeks	Measured on exercise cardiopulmonary stress test

Secondary Outcome Measures

Name	Time	Method
Resting Wedge Pressure	4 weeks	Assessed with right heart cath
Peak Oxygen Uptake	4 weeks
Resting Central Venous Pressure	4 weeks	Assessed with right heart cath
Resting Pulmonary Arterial Pressure	4 weeks	Assessed on right heart catheterization
Dyspnea - Visual Analog Scale (VAS)	4 weeks	The VAS for dyspnea has a range of 0 to 100, where 0 corresponds to the patient's subjective feeling of "I Can Breathe Normally" and a score of 100 corresponds to "I Can't Breathe At All."

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States